VCV000592147.12 - ClinVar

NM_001983.4(ERCC1):c.796G>A (p.Ala266Thr)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001983.4(ERCC1):c.796G>A (p.Ala266Thr)

Variation ID: 592147 Accession: VCV000592147.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.32 19: 45413724 (GRCh38) [ NCBI UCSC ] 19: 45916982 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 9, 2018	Oct 8, 2024	Jan 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001983.4:c.796G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001974.1:p.Ala266Thr	missense
NM_001166049.2:c.724G>A	NP_001159521.1:p.Ala242Thr	missense
NM_001369408.1:c.796G>A	NP_001356337.1:p.Ala266Thr	missense
NM_001369409.1:c.796G>A	NP_001356338.1:p.Ala266Thr	missense
NM_001369410.1:c.724G>A	NP_001356339.1:p.Ala242Thr	missense
NM_001369411.1:c.724G>A	NP_001356340.1:p.Ala242Thr	missense
NM_001369412.1:c.796G>A	NP_001356341.1:p.Ala266Thr	missense
NM_001369413.1:c.796G>A	NP_001356342.1:p.Ala266Thr	missense
NM_001369414.1:c.796G>A	NP_001356343.1:p.Ala266Thr	missense
NM_001369415.1:c.796G>A	NP_001356344.1:p.Ala266Thr	missense
NM_001369416.1:c.796G>A	NP_001356345.1:p.Ala266Thr	missense
NM_001369417.1:c.724G>A	NP_001356346.1:p.Ala242Thr	missense
NM_001369418.1:c.724G>A	NP_001356347.1:p.Ala242Thr	missense
NM_001369419.1:c.724G>A	NP_001356348.1:p.Ala242Thr	missense
NM_202001.3:c.796G>A	NP_973730.1:p.Ala266Thr	missense
NC_000019.10:g.45413724C>T
NC_000019.9:g.45916982C>T
NG_015839.2:g.70105G>A
LRG_305:g.70105G>A
LRG_305t1:c.796G>A	LRG_305p1:p.Ala266Thr

... more HGVS ... less HGVS

Protein change

A266T, A242T

Other names

Canonical SPDI

NC_000019.10:45413723:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00180 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00150

Trans-Omics for Precision Medicine (TOPMed) 0.00157

1000 Genomes Project 0.00180

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00185

1000 Genomes Project 30x 0.00203

The Genome Aggregation Database (gnomAD), exomes 0.00037

Links

dbSNP: rs3212977 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ERCC1		-	-	GRCh38 GRCh37	126	193

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cerebrooculofacioskeletal syndrome 4	Uncertain significance (1)	no assertion criteria provided	Aug 9, 2018	RCV000723350.1
not provided	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Jan 25, 2024	RCV000885540.10
ERCC1-related disorder	Likely benign (1)	no assertion criteria provided	Jun 6, 2022	RCV003945773.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Aug 12, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001871387.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on … (more) Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function (less)
Likely benign (Jan 25, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001028992.3 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Uncertain significance (Aug 09, 2018)	no assertion criteria provided Method: clinical testing	Cerebrooculofacioskeletal syndrome 4 Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV000854749.1 First in ClinVar: Dec 09, 2018 Last updated: Dec 09, 2018
Likely benign (Jun 06, 2022)	no assertion criteria provided Method: clinical testing	ERCC1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004760715.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs3212977 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_001983.4(ERCC1):c.796G>A (p.Ala266Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs3212977 ...